Toward a More Nuanced Interpretation of Statistical Significance in Biomedical Research

EditorialStatistical significance is the bedrock of evidence-based medicine, crucial for decision-making and framing biomedical science policies. The emergence of complex data in many disciplines, resulting from the analysis of large datasets, has amplified the popularity of p-values. Its simplicity allows investigators to conclude and disseminate their research findings in a manner understood by most. Thus, obtaining a p-value that indicates “statistical significance” against the null hypothesis is often required for publishing in medical journals. However, it creates challenges due to nonreproducibility, misuse and overinterpretation, which lead to serious methodological errors. This article aims to draw biomedical researchers' attention toward the appropriate use of p-values in clinical decision-making

Rapid screening and distribution of bioactive compounds in different parts of Berberis petiolaris using direct analysis in real time mass spectrometry

AbstractBerberis petiolaris Wall. ex G. Don, an unexplored medicinal plant belonging to the family Berberidaceae, is a large deciduous shrub found in Western Himalaya between 1800–3000m. Chemical profiling of fruit, leaf, root and stem was done by direct analysis in real time mass spectrometry followed by multivariate analysis for discrimination among the plant parts. The bioactive compounds, including magnoflorine, berberine, jatrorrhizine, thalifendine/berberrubine, demethyleneberberine, reticuline, 8-oxoberberine, N-methyltetrahydroberberine, tetrahydropalmatine, tetrahydroberberine and palmatine, were identified by their exact mass measurement and the corresponding molecular formula of each compound. A comparative study of distribution pattern for all these bioactive alkaloids showed qualitative and quantitative variations in different parts of B. petiolaris. Principal component analysis clearly discriminated each part of B. petiolaris plant

Digital Education for Health Professions on Smoking Cessation Management:Systematic Review by the Digital Health Education Collaboration

BACKGROUND: Tobacco smoking, one of the leading causes of preventable death and disease, is associated with 7 million deaths every year. This is estimated to rise to more than 8 million deaths per year by 2030, with 80% occurring in low- and middle-income countries. Digital education, teaching, and learning using digital technologies have the potential to increase educational opportunities, supplement teaching activities, and decrease distance barriers in health professions education. OBJECTIVE: The primary objective of this systematic review was to evaluate the effectiveness of digital education compared with various controls in improving learners' knowledge, skills, attitudes, and satisfaction to deliver smoking cessation therapy. The secondary objectives were to assess patient-related outcomes, change in health professionals' practice or behavior, self-efficacy or self-rated competence of health professionals in delivering smoking cessation therapy, and cost-effectiveness of the interventions. METHODS: We searched 7 electronic databases and 2 trial registers for randomized controlled trials published between January 1990 and August 2017. We used gold standard Cochrane methods to select and extract data and appraise eligible studies. RESULTS: A total of 11 studies (number of participants, n=2684) were included in the review. All studies found that digital education was at least as effective as traditional or usual learning. There was some suggestion that blended education results in similar or greater improvements in knowledge (standardized mean difference, SMD=0.19, 95% CI -0.35 to 0.72), skill (SMD=0.58, 95% CI 0.08-1.08), and satisfaction (SMD=0.62, 95% CI 0.12-1.12) compared with digital education or usual learning alone. There was also some evidence for improved attitude (SMD=0.45, 95% CI 0.18-0.72) following digital education compared with usual learning. Only 1 study reported patient outcomes and the setup cost of blended education but did not compare outcomes among groups. There were insufficient data to investigate what components of the digital education interventions were associated with the greatest improvements in learning outcomes. CONCLUSIONS: The evidence suggests that digital education is at least as effective as usual learning in improving health professionals' knowledge and skill for delivering smoking cessation therapy. However, limitations in the evidence base mean that these conclusions should be interpreted with some caution. TRIAL REGISTRATION: PROSPERO CRD42016046815; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=46815

Venous thromboembolism is linked to severity of disease in COVID-19 patients: A systematic literature review and exploratory meta-analysis

PURPOSE: Coronavirus disease-2019 (COVID-19) may predispose to venous thromboembolism (VTE) and arterial thromboembolism because of excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. Thus, in this meta-analysis, we aim to assess the association of VTE with the severity of COVID-19 disease.METHODS: A literature search was conducted on PubMed and Cochrane Central Register of Controlled Trials using the keywords "COVID-19 and thromboembolism" and "COVID-19 and embolism," till 20 February 2021. Thirteen studies including 6648 COVID-19 patients were incorporated in this systematic review and exploratory meta-analysis. RESULTS: The analysis revealed nearly three times more risk than intensive care unit (ICU) care in patients with VTE compared to non-VTE patients (RR: 2.78; 95% CI: 1.75-4.39; P < .001; I2 : 65.1%). Patients with pulmonary embolism and deep vein thrombosis are at increased risk of being admitted to ICU (RR: 2.21; 95% CI: 1.86-2.61; P < .001; I2 : 41.2%) and (RR: 2.69; 95% CI: 2.37-3.06; P < .001; I2 : 0.0%), respectively. The quality assessment indicated that the included studies were of fair quality. ONCLUSIONS: Our findings suggest that VTE either deep vein thrombosis or pulmonary embolism may have a negative effect on the health status of COVID-19 patients. This study highlights the need to consider measures for reducing thromboembolism risk amongst COVID-19 patients

Birthing practices of traditional birth attendants in South Asia in the context of training programmes

Traditional Birth Attendants (TBA) training has been an important component of public health policy interventions to improve maternal and child health in developing countries since the 1970s. More recently, since the 1990s, the TBA training strategy has been increasingly seen as irrelevant, ineffective or, on the whole, a failure due to evidence that the maternal mortality rate (MMR) in developing countries had not reduced. Although, worldwide data show that, by choice or out of necessity, 47 percent of births in the developing world are assisted by TBAs and/or family members, funding for TBA training has been reduced and moved to providing skilled birth attendants for all births. Any shift in policy needs to be supported by appropriate evidence on TBA roles in providing maternal and infant health care service and effectiveness of the training programmes. This article reviews literature on the characteristics and role of TBAs in South Asia with an emphasis on India. The aim was to assess the contribution of TBAs in providing maternal and infant health care service at different stages of pregnancy and after-delivery and birthing practices adopted in home births. The review of role revealed that apart from TBAs, there are various other people in the community also involved in making decisions about the welfare and health of the birthing mother and new born baby. However, TBAs have changing, localised but nonetheless significant roles in delivery, postnatal and infant care in India. Certain traditional birthing practices such as bathing babies immediately after birth, not weighing babies after birth and not feeding with colostrum are adopted in home births as well as health institutions in India. There is therefore a thin precarious balance between the application of biomedical and traditional knowledge. Customary rituals and perceptions essentially affect practices in home and institutional births and hence training of TBAs need to be implemented in conjunction with community awareness programmes

A Randomized Waitlist-Controlled Trial of an Intergenerational Arts and Heritage-Based Intervention in Singapore: Project ARTISAN

Loneliness has become a global major public health concern, with detrimental effects to the young and old. ARTISAN (Aspiration and Resilience Through Intergenerational Storytelling and Art-based Narratives) is a 5-week, 15-h participatory art and group-based intervention that focuses on resilience building and loneliness alleviation among the young and old through a structured multimodal framework held at a museum space. Developed with a Participatory Action Research (PAR) approach, this intervention is evaluated using an open-label waitlist randomized controlled trial design (RCT) comprised of community-dwelling youth and older adults randomized into an intervention group (n = 35) or a waitlist-control group (n = 33). Participants were assessed on standardized self-reported psychometric measures including loneliness, resilience, quality of life, social support, life satisfaction and national identity at three time points. Qualitative data generated during each intervention session as well as acceptability focus groups were recorded and transcribed. Linear mixed modeling analyses revealed that participants in the intervention group experienced improvements in life satisfaction compared to participants in the waitlist-control group (95% CI: 0.22 to 0.77, p &amp;lt; 0.001, Cohen's d = 0.53) immediately after the completion of ARTISAN. Subgroup analyses for youth participants indicated improvements in quality of life (95% CI: 0.16 to 0.52, p &amp;lt; 0.001, d = 1.31) and national identity (95% CI: 0.18 to 0.80, p = 0.002, d = 0.43) in comparison to the waitlist-control group. At 5-weeks follow-up, the intervention group participants continued to experience high levels of life satisfaction (95% CI: 0.04 to 0.42, p = 0.017, d = 0.47), enhancements in resilience (95% CI: 0.07 to 0.55, p = 0.011, d = 0.46), as well as a significant reduction in loneliness (95% CI: −0.34 to −0.08, p = 0.001, d = 0.61) compared to baseline, reflecting the effectiveness and positive residual effects of the ARTISAN intervention. Similarly, the qualitative findings provided support for the intervention and additional insights to the quantitative findings. This holistic intervention framework that integrates stories, arts and heritage for bridging and empowering lives fills a critical gap in knowledge and practice between the arts, health and citizenship, paving the way for further research in creating a more caring and inclusive society with the arts

Identifying carers in general practice (STATUS QUO): a multicentre, cross-sectional study in England

ObjectivesTo determine General Practice (GP) recording of carer status and the number of patients self-identifying as carers, while self-completing an automated check-in screen prior to a GP consultation.DesignA descriptive cross-sectional study.Setting11 GPs in the West Midlands, England. Recruitment commenced in September 2019 and concluded in January 2020.ParticipantsAll patients aged 10 years and over, self-completing an automated check-in screen, were invited to participate during a 3-week recruitment period.Primary and secondary outcome measuresThe current coding of carers at participating GPs and the number of patients identifying themselves as a carer were primary outcome measures. Secondary outcome measures included the number of responses attained from automated check-in screens as a research data collection tool and whether carers felt supported in their carer role.Results80.3% (n=9301) of patients self-completing an automated check-in screen participated in QUantifying the identification Of carers in general practice (STATUS QUO Study) (62.6% (n=5822) female, mean age 52.9 years (10-98 years, SD=20.3)). Prior to recruitment, the clinical code used to denote a carer was identified in 2.7% (n=2739) of medical records across the participating GPs.10.1% (n=936) of participants identified themselves as a carer. They reported feeling supported with their own health and social care needs: always 19.3% (n=150), a lot of the time 13.2% (n=102), some of the time 40.8% (n=317) and never 26.7% (n=207).ConclusionsMany more participants self-identified as a carer than were recorded on participating GP lists. Improvements in the recording of the population's caring status need to be actioned, to ensure that supportive implementation strategies for carers are effectively received. Using automated check-in facilities for research continues to provide high participation rates

Systematic review identifies the design and methodological conduct of studies on machine learning-based prediction models

Background and ObjectivesWe sought to summarize the study design, modelling strategies, and performance measures reported in studies on clinical prediction models developed using machine learning techniques.MethodsWe search PubMed for articles published between 01/01/2018 and 31/12/2019, describing the development or the development with external validation of a multivariable prediction model using any supervised machine learning technique. No restrictions were made based on study design, data source, or predicted patient-related health outcomes.ResultsWe included 152 studies, 58 (38.2% [95% CI 30.8–46.1]) were diagnostic and 94 (61.8% [95% CI 53.9–69.2]) prognostic studies. Most studies reported only the development of prediction models (n = 133, 87.5% [95% CI 81.3–91.8]), focused on binary outcomes (n = 131, 86.2% [95% CI 79.8–90.8), and did not report a sample size calculation (n = 125, 82.2% [95% CI 75.4–87.5]). The most common algorithms used were support vector machine (n = 86/522, 16.5% [95% CI 13.5–19.9]) and random forest (n = 73/522, 14% [95% CI 11.3–17.2]). Values for area under the Receiver Operating Characteristic curve ranged from 0.45 to 1.00. Calibration metrics were often missed (n = 494/522, 94.6% [95% CI 92.4–96.3]).ConclusionOur review revealed that focus is required on handling of missing values, methods for internal validation, and reporting of calibration to improve the methodological conduct of studies on machine learning–based prediction models

Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study

ObjectivesColchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol.MethodsWe conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997–30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated.ResultsFrom 01/04/1997–30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD.ConclusionPeople were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol